Selenium carbanions

The Peterson reaction has two more advantages over the Wittig reaction 1. it is sometimes less vulnerable to sterical hindrance, and 2. groups, which are susceptible to nucleophilic substitution, are not attacked by silylated carbanions. The introduction of a methylene group into a sterically hindered ketone (R.K. Boeckman, Jr., 1973) and the syntheses of olefins with sulfur, selenium, silicon, or tin substituents (D. Seebach, 1973 B.T. Grdbel, 1974, 1977) illustrate useful applications. The reaction is, however, more limited and time consuming than the Wittig reaction, since metallated silicon derivatives are difficult to synthesize and their reactions are rarely stereoselective (T.H. Chan, 1974 ... 

For reviews of sulfur-containing carbanions, see Oae, S. Uchida, Y. in Patai Rappoport Stirling The Chemistry ofSulphones and Sulphoxides, Wiley NY, 1988, p. 583 Wolfe, S. in Bemardi Csizmadia Mangini Organic Sulfur Chemistry Elsevier, NY, 1985, p. 133 Block, E. Reactions ofOrganosulfur Compounds Academic Press NY, 1978, p. 42 Durst, T. Viau, R. Intra-Sci. Chem. Rep., 1973, 7 (3), 63. For a review of selenium-stabilized carbanions, see Reich, H.J. in Liotta Organoselenium Chemistry Wiley NY, 1987, p. 243. For support for this theory, see Wolfe, S. LaJohn, L.A. Bemardi, F Mangini, A. Tonachini, G. Tetrahedron Lett., 1983, 24, 3789 Wolfe, S. Stolow, A. LaJohn, L.A. Tetrahedron Lett., 1983, 24, 4071. 

Pohnert G (2004) Chemical Defense Strategies of Marine. 239 179-219 Ponthieux S, Paulmier C (2000) Selenium-Stabilized Carbanions. 208 113-142 Port M,see Idee J-M (2002) 222 151-171... 

Opposite to that found for a-lithiated ethers, carbanionic centers in the a-position to a sulfur atom are configurationally unstable. The lifetime at 78 °C is in the order of seconds only, even shorter than with the homologous selenium compounds54. In the latter case, at — 120°C configurational stability has been observed in one case for at least some hours55. 

Cyclopropanations are known for several other carbanionic intermediates of the general type (7), in which the substituent G is ultimately lost as an anionic leaving group in the last step of the ring-forming pathway (see Scheme 3 above). The substituent G is most often a functional group based upon sulfur, selenium or nitrogen. Halide-substituted derivatives probably react via the a-elimination pathway in most cases (see Section 4.6.3.1), but in some reactions with electron deficient alkenes as substrates, the normal order of steps may be altered (e.g. Table 10, ref. 162). 

Reaction of 2,5-dimethoxycarbonyl-3,4-dicyanomethylthiophene 260, which is readily available from the corresponding dibromide 259 by reaction with buffered potassium or sodium cyanide, with thionyl chloride and selenium oxychloride, gave thieno[3,4-c]thiophene 255 and selenolo[3,4-c]thiophene 258, respectively (.Scheme 50) [79], This is the first example of the reaction of thionyl chloride with a carbanion acting as an S-transfer agent. 

It was found (2 3) that the best synthetic approach to phosphonates containing sulfur and selenium in the a-position is based on the reaction of elemental sulfur and selenium with a-phos-phonate carbanions. It is interesting to note that, in contrast to sulfur, selenium may be added in this way to the tertiary carbon atom. 

Cleavage of a carbon to sulfur bond by a lithium reagent is a well known entry to organolithium reagents. This process has been used to synthesize a-nitrogen carbanions, and hence SMA derivatives.67 165 This study has been extended to tellurium and selenium starting materials as well.166... 

Besides the use of electrophilic or nucleophilic selenium reagents in synthesis, selenium has another advantage. It can stabilize adjacent carbanions or carbocations. While the deprotonation of selenides is difficult, the corresponding diselenoacetals can be used as efficient precursors through the cleavage of one of the carbon-selenium bonds. The chemistry of selenium-stabilized carbanions and carbocations is outlined in Section 9.11.2.3. 

Selenium-stabilized carbanions are recognized as important intermediates in organic synthesis. Their formation and reactivity as nucleophilic reagents were studied some time ago and general aspects are decribed in earlier reviews.46,47 More detailed descriptions and reactions of a-selanylalkyl lithiums and potassium analogs were presented in other reviews.195... 

Various applications of selenium-stabilized carbanions in synthesis have been reported. The mixed acetal 108 derived from benzaldehyde was efficiently metalated by KDA in THF. The a-methoxy-a-methylselanyl benzyl-potassium compound 109 is stable at low temperatures (—78 °C) and reacted with a variety of electrophiles. The reaction products 110, still mixed acetals, are obtained in good yields as shown in Table 3 (Scheme 25).196... 

The addition of a selenium-stabilized carbanion to an electrophile can be followed by another reaction as selenones are good leaving groups. a-Selenonylalkyl compounds 111 can be deprotonated using potassium tert-butoxide. Reactions with a,/ -unsaturated / r/-butyl esters lead to cyclopropane derivatives 112 in good yields (Scheme 26).197... 

Figure 5 Precursors for the synthesis of selenium-stabilized carbanions from 123.

The formation of /3-hydroxyselenides through the reaction of a selenium-stabilized carbanion with carbonyl compounds has been extensively used also in the context of natural product synthesis. The phenylselenoalkyllithium compound 115 was reacted with aldehyde 116 to afford /3-hydroxyselenide 117. In a radical cyclization cascade the tricyclic molecule 118 was generated in good yields and subsequent transformations led to the synthesis of pentalenene 119 (Scheme 28).1 9 Also other natural products like zizaene and khusimone have been synthesized via a similar route.200... 

Selenium-stabilized carbanions can be also generated by 1,4-addition of nucleophilic reagents to a-selanyl a,[3-unsaturated carbonyl compounds. The conjugate addition of trialkylsilyllithium compounds to 133, followed by reaction with allyl iodide, afforded the addition products 134 with good m-stereoselectivity (R = Me dr 86 14 R = Ph dr 94 6) (Scheme 34).214 The addition of lithium dialkylcuprates to 2-phenylselanylcycloalk-2-enones has also been used for the synthesis of natural products.215,216... 

Also other functionalities can be present in selenium-stabilized carbanions. The choice of base for the deprotonation of compounds 135 is crucial and sometimes side-products are formed. a-Cyano substituted compounds 135a (R = CN) are known 217 a-phosphono compounds 135b (R = P(0)(0Et)2)218 and also a-arenesulfanyl componds 135c (R = S02Ar) have been used in the synthesis of selenium-stabilized carbanions (Figure 6). 

Figure 6 Precursor molecules for selenium stabilized carbanions.

The ability of carbanions to react with elemental selenium can be advantageously used for the synthesis of selenocarbonyl compounds. For example, sulfur ylides 201 (E = +SMe2) have been reacted with elemental selenium to generate the corresponding selenocarbonyl compounds 202 (Scheme 59).374,375 But Staudinger selenylation also has been applied to the synthesis of selenoketones 202 from phosphorus ylides 201 (E = +PPh3), which have been trapped by dienes in hetero-Diels-Alder reactions.376-383... 

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